Verification of microRNA expression in human endometrial adenocarcinoma

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Background:
MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1.

Methods:
Twenty-five miRNAs that were previously identified as differentially expressed were subjected to further analysis using qPCR. To investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection with a synthetic mir-34a mimic and a mir-34a inhibitor.

Results:
Of the 25 validated miRNAs, seven were down-regulated and 18 were up-regulated compared to normal endometrium, which was fully consistent with our previous findings. In addition, the up-regulation of mir-34a led to a significant decrease in mRNA levels of NOTCH1 and DLL1, while down-regulation led to a significant increase in mRNA levels of these two genes.

Conclusions:
We verified both up-regulated and down-regulated miRNAs in the tumor samples, indicating various roles of microRNAs during tumor development. Mir-34a functions as a regulator by decreasing the expression of NOTCH1 and DLL1. Our study is the first to identify a correlation between mir-34a and its target genes NOTCH1 and DLL1 in endometrial adenocarcinoma.

Keywords:
Endometrial adenocarcinoma microRNA mir-34a Target genes

Autoři: Sanja Jurcevic; Karin Klinga-Levan; Björn Olsson; Katarina Ejeskär
Působiště autorů: Systems Biology Research Centre-Biomedical genetics, School of Bioscience, University of Skövde, Skövde, Sweden. ¹; Systems Biology Research Centre-Bioinformatics, School of Bioscience, University of Skövde, Skövde, Sweden. ²
Vyšlo v časopise: BMC Cancer 2016, 16:261
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12885-016-2296-z

© 2016 Jurcevic et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2296-z

Souhrn

Keywords:
Endometrial adenocarcinoma microRNA mir-34a Target genes

Zdroje

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